Disaccharides generated from heparan sulphate or heparin modulate chemokine-induced T-cell adhesion to extracellular matrix

R. Hershkoviz, H. Schor, A. Ariel, I. Hecht, I. R. Cohen, O. Lider, L. Cahalon

Research output: Contribution to journalArticlepeer-review


We have found previously that disaccharides (DS) enzymatically generated from heparin or heparan sulphate can modulate tumour necrosis factor-α (TNF- α) secretion from immune cells in vitro and cell-mediated immune reactions in vivo. Here, we show that such DS can modulate the adhesion and migration of human T cells. We found that certain heparin- and heparan sulphate-derived DS induced, in a dose-dependent manner, the adhesion of human T Cells to both extracellular matrix (ECM) and immobilized fibronectin (FN); maximal T-cell adhesion occurred with 1 ng/ml of DS. The levels of T-cell adhesion to ECM that were induced by the tested DS molecules resembled those induced by the prototypic chemokine, macrophage inflammatory protein 1β (MIP-1β). However, the kinetics of DS-induced T-cell adhesion to FN resembled that induced by phorbol myristate acetate (PMA), but not that induced by MIP-1β. This adhesion appeared to involve β1 integrin recognition and activation, and was associated with specific intracellular activation pathways. Although a first exposure of T cells to certain DS molecules appeared to result in cell adhesion, a subsequent exposure of T cells to pro-adhesive chemokines, such as MIP-1β or RANTES, but not to other pro-adhesive stimuli, for example interleukin-2 or CD3 cross-linking, resulted in inhibition of T-cell adhesion to and chemotactic migration through FN. Hence, we propose that the breakdown products of tissues generated by inflammatory enzymes are part of an intrinsic functional programme, and not necessarily molecular waste. Moreover, because the DS molecules exert their modulatory functions within a limited time, it appears that the historical encounters of the tissue- invading cells with the constituents of inflamed loci may dictate the cells' behaviour upon subsequent exposure to proinflammatory mediators.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
Issue number1
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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